FDA approves immune-boosting therapy for prostate cancer

It marks the agency’s first approval of an immunotherapy treatment for cancer, a move toward a new approach to battling many forms of the disease.

By Thomas H. Maugh II, Los Angeles Times

8:15 p.m. EDT, April 29, 2010

The Food and Drug Administration approved a new immune-boosting therapy for prostate cancer on Thursday, the first therapeutic vaccine for cancer ever approved by the agency. The approval opens the door to a whole new approach to cancer therapy, adding a unique weapon to the arsenal of oncologists.

The vaccine, Provenge, has been shown to extend survival in patients with advanced prostate cancer by four months, more than twice as long as chemotherapy, and to increase three-year survival by 38%.

"A lot of people have been working in labs, biotechs and pharma companies looking for a proof of principle" that immunotherapy works against cancer, said Dr. David I. Quinn, medical director of the USC Norris Cancer Hospital. "This is the proof of principle."

Patient advocates who have been fighting for Provenge's approval since the FDA initially rejected the drug in 2007 were overjoyed.

"I'm crying happy tears," said Jan Manarite, who runs the Florida help line for the Prostate Cancer Research Institute, an advocacy organization. Manarite, who organized a march on Capitol Hill after the earlier FDA rejection and whose husband has been fighting prostate cancer for a decade, said cancer patients have been longing for access to an immunotherapy treatment.

"They want something that boosts the immune system and doesn't have a lot of side effects," she said.

About 192,000 new cases of prostate cancer were diagnosed in the United States in 2009, making it the second most common type of cancer in men after lung cancer, according to the National Cancer Institute. About 27,000 men died from it last year.

The therapy has been a long time coming.

It has been two decades since immunologist Edgar G. Engleman of the Stanford University School of Medicine first discovered a way to harness the body's immune cells to fight prostate cancer. Along the way, several other highly touted vaccines against melanoma and lung and prostate cancer, among others, appeared to offer great promise only to fall by the wayside when clinical trials did not support their initial successes.

Engleman's aim was to ramp up the body's immune system by exposing it to proteins that the cancer cells made, priming the body to fight the cancer more fiercely. First he collected specialized immune cells called dendritic cells from the patient's blood. Then he mixed them with proteins collected from the surface of prostate tumor cells and injected them back into the patient in three doses at two-week intervals.

He eventually co-founded the Seattle company now known as Dendreon Corp. to bring the vaccine to market.

Its road has been rocky.

Provenge's marketing appeared imminent in 2007 when an advisory panel for the FDA recommended its approval. But agency officials were concerned that, even though the vaccine extended lifespan in men with metastatic cancer who did not respond to hormone-deprivation therapy (the first-line treatment approach in prostate cancer), it did not slow tumor growth.

The agency also said that too few men had been studied and asked Dendreon to perform a larger trial in more than 500 men. Results from that trial were presented this year at the annual meeting of the American Society of Clinical Oncology, or ASCO, by Dr. Philip Kantoff of the Dana-Farber Cancer Institute in Boston.

Kantoff and co-workers found that, compared with a placebo, Provenge extended the median survival of patients from 21.7 months to 25.8 months. Though 4.1 months may not seem like much, the only approved chemotherapy for advanced prostate cancer — Taxotere, known generically as docetaxel — extends survival by a little more than two months.

Taxotere is also associated with powerful side effects, including bone and muscle pain, allergic reactions, decreases in white and red blood cell counts and nerve damage. The main side effects of Provenge include chills, fever, fatigue, joint ache and headache.

The approval of Provenge had been widely expected following the ASCO meeting because the results of Kantoff's study "met the expectations that the FDA and the company had agreed to," said Dr. Stanton Gerson, director of the University Hospitals Ireland Cancer Center in Cleveland and a member of the FDA advisory committee.

The biggest drawback to the vaccine may be its cost, which analysts estimate will be about $70,000 to $100,000 for a course of treatment. Because many insurance companies require a co-payment of about 20%, many families may be hard-pressed to pay for the drug.

Part of the reason for the high cost is that white blood cells must be removed from each patient by a process called plasmapheresis and sent to a laboratory where they will be converted into an individualized vaccine. "It will be a learning process for patients and physicians," Manarite said.

Meanwhile, researchers are conducting trials to see if they can improve the clout of the vaccine by giving it to patients earlier in the course of the disease and in combination with chemotherapy.